RETASPIMYCIN HYDROCHLORIDE

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C31H45N3O8.ClH
Molecular Weight	624.165
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CO[C@H]1C[C@H](C)CC2=C(O)C(NC(=O)\C(C)=C\C=C[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@H]1O)=CC(O)=C2NCC=C

InChI

InChIKey=OIRUWDYJGMHDHJ-AFXVCOSJSA-N

InChI=1S/C31H45N3O8.ClH/c1-8-12-33-26-21-13-17(2)14-25(41-7)27(36)19(4)15-20(5)29(42-31(32)39)24(40-6)11-9-10-18(3)30(38)34-22(28(21)37)16-23(26)35;/h8-11,15-17,19,24-25,27,29,33,35-37H,1,12-14H2,2-7H3,(H2,32,39)(H,34,38);1H/b11-9-,18-10+,20-15+;/t17-,19+,24+,25+,27-,29+;/m1./s1

HIDE SMILES / InChI

Molecular Formula	C31H45N3O8
Molecular Weight	587.7043
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	6 / 6
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.ncbi.nlm.nih.gov/pubmed/17090671
Curator's Comment: Description was created based on several sources, including http://www.gistsupport.org/treatments-for-gist/emerging-treatments/hsp90-inhibitors/ipi-504-retaspimycin.php and https://newdrugapprovals.org/2015/10/27/ipi-504-retaspamycin-retaspimycin/

Retaspimycin (IPI-504) was previously under development by manufacturer Infinity Pharmaceuticals in conjunction with MedImmune, a part of AstraZeneca. Retaspimycin is a small-molecule inhibitor of heat shock protein 90 (HSP90) with antiproliferative and antineoplastic activities. Retaspimycin binds to and inhibits the cytosolic chaperone functions of HSP90, which maintains the stability and functional shape of many oncogenic signaling proteins and may be overexpressed or overactive in tumor cells. Retaspimycin-mediated inhibition of HSP90 promotes the proteasomal degradation of oncogenic signaling proteins in susceptible tumor cell populations, which may result in the induction of apoptosis. Orphan drug designation was assigned to the compound by the FDA for the treatment of gastrointestinal stromal cancer (GIST). Infinity Pharmaceuticals has discontinued the development of retaspimycin (IPI-504) an inhibitor of the HSP-90) complex, for the treatment of cancer due to lack of efficacy in 1913.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Heat shock protein HSP90 35 Target ID: CHEMBL2095165 Sources: http://www.ncbi.nlm.nih.gov/pubmed/17090671	Inhibitor 8504		63.0 nM [EC50]

Conditions

Condition	Modality	Highest Phase	Product
Gastrointestinal stromal tumor 20 Sources: https://clinicaltrials.gov/ct2/show/NCT00688766	Primary	Phase III 665	Unknown Approved Use Unknown
Prostate cancer 186 Sources: https://clinicaltrials.gov/ct2/show/NCT00564928	Primary	Phase II 1147	Unknown Approved Use Unknown
Advanced dedifferentiated liposarcoma 2 Sources: https://clinicaltrials.gov/ct2/show/NCT00969917	Primary	Phase II 1147	Unknown Approved Use Unknown
KRAS mutant non-small cell lung cancer 2 Sources: https://clinicaltrials.gov/ct2/show/NCT01427946	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
7800 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21762967	400 mg/m² single, intravenous dose: 400 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		RETASPIMYCIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4637 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21851215	400 mg/m² 2 times / week single, intravenous dose: 400 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		RETASPIMYCIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
11712 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21762967	400 mg/m² single, intravenous dose: 400 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		RETASPIMYCIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5030 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21851215	400 mg/m² 2 times / week single, intravenous dose: 400 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		RETASPIMYCIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.27 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21762967	400 mg/m² single, intravenous dose: 400 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		RETASPIMYCIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21851215	400 mg/m² 2 times / week single, intravenous dose: 400 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		RETASPIMYCIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
500 mg/m2 2 times / week multiple, intravenous Highest studied dose Dose: 500 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 500 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/24045182	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/24045182	DLT: headache, myalgia... Dose limiting toxicities: headache (grade 3, 16.7%) myalgia (grade 3, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/24045182
400 mg/m2 2 times / week multiple, intravenous MTD Dose: 400 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 400 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/21762967	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21762967	Disc. AE: AST increased, ALT increased... AEs leading to discontinuation/dose reduction: AST increased (grade 3, 5.3%) ALT increased (grade 3, 5.3%) Hepatic failure (grade 5, 5.3%) Hyperglycemia (grade 5, 5.3%) ketoacidosis (grade 5, 5.3%) Multi-organ failure (grade 5, 5.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/21762967
400 mg/m2 2 times / week multiple, intravenous MTD Dose: 400 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 400 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/24045182	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/24045182	DLT: Intracerebral hemorrhage... Other AEs: Hepatic failure, Acute renal failure... Dose limiting toxicities: Intracerebral hemorrhage (grade 5, 16.7%) Other AEs: Hepatic failure (grade 5, 16.7%) Acute renal failure (grade 5, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/24045182

AEs

AE	Significance	Dose	Population
headache	grade 3, 16.7% DLT	500 mg/m2 2 times / week multiple, intravenous Highest studied dose Dose: 500 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 500 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/24045182	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/24045182
myalgia	grade 3, 16.7% DLT	500 mg/m2 2 times / week multiple, intravenous Highest studied dose Dose: 500 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 500 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/24045182	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/24045182
ALT increased	grade 3, 5.3% Disc. AE	400 mg/m2 2 times / week multiple, intravenous MTD Dose: 400 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 400 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/21762967	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21762967
AST increased	grade 3, 5.3% Disc. AE	400 mg/m2 2 times / week multiple, intravenous MTD Dose: 400 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 400 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/21762967	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21762967
Hepatic failure	grade 5, 5.3% Disc. AE	400 mg/m2 2 times / week multiple, intravenous MTD Dose: 400 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 400 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/21762967	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21762967
Hyperglycemia	grade 5, 5.3% Disc. AE	400 mg/m2 2 times / week multiple, intravenous MTD Dose: 400 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 400 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/21762967	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21762967
Multi-organ failure	grade 5, 5.3% Disc. AE	400 mg/m2 2 times / week multiple, intravenous MTD Dose: 400 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 400 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/21762967	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21762967
ketoacidosis	grade 5, 5.3% Disc. AE	400 mg/m2 2 times / week multiple, intravenous MTD Dose: 400 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 400 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/21762967	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21762967
Acute renal failure	grade 5, 16.7%	400 mg/m2 2 times / week multiple, intravenous MTD Dose: 400 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 400 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/24045182	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/24045182
Hepatic failure	grade 5, 16.7%	400 mg/m2 2 times / week multiple, intravenous MTD Dose: 400 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 400 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/24045182	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/24045182
Intracerebral hemorrhage	grade 5, 16.7% DLT, Disc. AE	400 mg/m2 2 times / week multiple, intravenous MTD Dose: 400 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 400 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/24045182	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/24045182

Sourcing

Vendor/Aggregator	ID	URL
AbMole Bioscience	M3683	http://www.abmole.com/products/retaspimycin.html
Achemtek	0102-013797	http://www.achemtek.com/857402-23-4
Alsachim	4612	http://www.alsachim.com/product-C5959-glo.bal-view.html
ApexBio Technology	A3756	http://www.apexbt.com/retaspimycin.html
BioChemPartner	BCP06481	http://www.biochempartner.com/857402-23-4-BCP06481
BioCrick	BCC1889	http://www.biocrick.com/Retaspimycin-BCC1889.html
BOC Sciences	857402-23-4	https://www.bocsci.com/retaspimycin-cas-857402-23-4-item-99330.html
Chem Scene	CS-0651	http://www.chemscene.com/857402-23-4.html
ChemMol	49418536	http://www.chemmol.com/chemmol/49418536.html
Clearsynth	CS-EK-02070	https://www.clearsynth.com/en/CSEK02070.html
eNovation Chemicals	D680329	https://www.enovationchem.com/ProductDetails.asp?ProductID=D680329
MedChem Express	HY-15263	https://www.medchemexpress.com/retaspimycin.html
MuseChem	I005151	https://www.musechem.com/product/I005151.html
OChem	29906	http://www.ocheminc.com/index.php?act=psearch&pid=402R234
Smolecule	S639259	https://www.smolecule.com/products/s639259
THE BioTek	bt-341427	https://www.thebiotek.com/product/others/bt-341427

PubMed

Title	Date	PubMed
HSP90 inhibition enhances antimitotic drug-induced mitotic arrest and cell death in preclinical models of non-small cell lung cancer.	2014	25542032
Development of 17-allylamino-17-demethoxygeldanamycin hydroquinone hydrochloride (IPI-504), an anti-cancer agent directed against Hsp90.	2006-11-14	17090671
Design, synthesis, and biological evaluation of hydroquinone derivatives of 17-amino-17-demethoxygeldanamycin as potent, water-soluble inhibitors of Hsp90.	2006-07-27	16854066

Patents

Sample Use Guides

In Vivo Use Guide

Retaspimycin (IPI-504) was administered intravenously at doses ranging from 90 to 500 mg/m(2) twice weekly for 2 weeks on/1 week off.

Route of Administration: Intravenous

In Vitro Use Guide

Human liver microsomes were incubated for 1 h at 37°C with 50 ug/ml Retaspimycin (IPI-504)

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:05:17 GMT 2025` Edited by `admin` on `Mon Mar 31 18:05:17 GMT 2025`
Record UNII	928Q33Q049
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

RETASPIMYCIN HYDROCHLORIDE

Official Name

English

RETASPIMYCIN HYDROCHLORIDE [MI]

Preferred Name

English

Retaspimycin hydrochloride [WHO-DD]

Common Name

English

IPI-504 HYDROCHLORIDE

Code

English

RETASPIMYCIN HYDROCHLORIDE [USAN]

Common Name

English

(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-13,20,22-TRIHYDROXY-8,14-DIMETHOXY-4,10,12,16- TETRAMETHYL-3-OXO-19-(PROP-2-ENYLAMINO)-2-AZABICYCLO(16.3.1)DOCOSA- 1(21),4,6,10,18(22),19-HEXEN-9-YL CARBAMATE HYDROCHLORIDE

Common Name

English

RETASPIMYCIN HCL

Common Name

English

GELDANAMYCIN, 18,21-DIDEHYDRO-17-DEMETHOXY-18,21-DIDEOXO-18,21-DIHYDROXY-17-(2- PROPENYLAMINO)-, MONOHYDROCHLORIDE

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

260608